Skin pigmentation can act as a “sponge” for some medications, potentially influencing the speed with which active drugs reach their intended targets, a pair of scientists report in a prospective paper published in the journal Human genomics.
Researchers argue that a considerable proportion of drugs and other compounds can bind to melanin pigments in the skin, leading to differences in the bioavailability and effectiveness of these drugs and other compounds in people with different skin tones.
“Our review article concludes that melanin, the pigment responsible for skin color, shows a surprising affinity for certain drug compounds,” said Simon Groen, assistant professor of evolutionary systems biology at the Institute for Integrative Genome Biology. University of California, Riverside. and co-author of the article. “The implications of melanin for drug safety and dosing have been largely overlooked, raising alarming questions about the effectiveness of standard dosing, as people vary widely in skin tone.” .
According to Groen and co-author Sophie Zaaijer, a UC Riverside-affiliated consultant and researcher who specializes in diversity, equity and inclusion (DEI) in preclinical R&D and clinical trials, current FDA guidelines for toxicity testing do not adequately address the impact of skin pigmentation. about drug interactions.
“This oversight is particularly concerning given the push for more diverse clinical trials, as outlined in the agency’s Diversity Action Plan,” Zaaijer said. “But current early-stage drug development practices still focus primarily on drug testing in white populations of northern European descent.”
In one example, researchers found evidence of nicotine’s affinity for skin pigments, which could affect smoking habits in people with a variety of skin tones and raise questions about the effectiveness of nicotine patches attached to skin. the skin to quit smoking.
“Are we inadvertently shortchanging smokers with darker skin tones if they turn to these patches in their attempts to quit smoking?” Groen said.
Groen and Zaaijer propose using a new workflow involving 3D human skin models with different levels of pigmentation that could offer pharmaceutical companies an efficient method to evaluate drug binding properties in different skin types.
“Skin pigmentation should be considered as a factor in safety and dosage estimates,” Zaaijer said. “We are on the brink of a transformative era in the biomedical industry, where embracing inclusion is no longer just an option but a necessity.”
According to researchers, skin pigmentation is just one example. Genetic variations among minority groups can lead to markedly different drug responses between races and ethnicities, affecting up to 20% of all medications, they said.
“However, our molecular understanding of these differences remains very limited,” Zaaijer said.
Researchers recognize that transformations that improve inclusion (spanning race, ethnicity, sex, and age) require a comprehensive review of all FDA guidelines on clinical endpoints to align with the FDA Action Plan. FDA Diversity.
“It is a monumental task that requires clear lines of communication between academics, industry researchers, clinicians and regulators,” Zaaijer said. “The future of medicine depends on our ability to connect these currently isolated operating teams.”
Researchers note that there will be a shift toward inclusive drug development, driven by a new law, the Omnibus Food and Drug Reform Act, enacted in 2022.
“The FDA recently released its draft guidelines,” Zaaijer said. “Once finalized in a few months, they will require consideration of patient diversity in clinical trials and preclinical R&D. The next step is to provide guidance on which pharmacokinetic variables should be tested in drug R&D projects.” in their search for equitable medicines.
The researchers hope to activate the pharmaceutical industry and academia to begin conducting systematic experimental evaluations in preclinical research regarding skin pigmentation and drug kinetics.
They also encourage patients, their advocacy groups, and clinical trial participants to ask questions related to the effectiveness and safety of medications specific to their ancestry, such as: “Has this medication been tested to see if it is safe for you?” people of different ancestral backgrounds, including mine? ” The researchers said doctors and pharmaceutical representatives should be able to provide an easy-to-understand document describing the results of the various tests.
They recognize that in the current state of drug development this will be difficult.
“In terms of risk profile testing, drugs are most often tested in one or a few human cell models that mostly come from donors of Northern European ancestry,” Zaaijer said. “The drugs are then tested in a rodent model. If these tests are successful, pharmaceutical companies take the drug into clinical trials. But are the drugs ready to be administered to a diverse group of patients if they have not been tested first? , for example? in human cell models of different ancestry? Would you bungee jump off a bridge if you knew the ropes had not been tested for your weight category? So why is this currently unlikely with medications?
Groen explained that in different ancestral origins certain genetic variants are more prevalent. Those variants can affect how a drug is metabolized and how it behaves in the body, he said.
“If different ancestral origins are taken into account in the early stages of drug discovery, then diverse groups of people may have more confidence in the drug development process and enroll in clinical trials because they will be better informed of any potential associated risks,” said. saying.